کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5547766 1556145 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In vitro evaluation of cytotoxicity and leishmanicidal activity of phthalimido-thiazole derivatives
ترجمه فارسی عنوان
ارزیابی سمیت سلولی و فعالیت لیشمانتیکیدی مشتقات فتالیمیدو تیزول در آزمایشگاهی
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی

It is estimated that the worldwide prevalence of leishmaniasis is around 12 million individuals in 80 countries, with 400,000 new cases per year. In the search for new leishmanicidal agents, the hybrid phthalimido-thiazoles have been identified as an important scaffold for drug design and discovery. The present study thus reports the in vitro activity of a series of phthalimido-thiazole derivatives. Cytotoxicity against a strain of L. infantum, Vero cells, J774 macrophages and peritoneal macrophages was evaluated, as well as nitric oxide (NO) production. Activity against amastigote and promastigote forms of L. infantum and microscopic changes in the parasite and intracellular targets of the parasite were achieved. The results show that the compounds arising from hybridization of phthalimide and 1,3-thiazole exhibit promising leishmanicidal activity. Compounds 2j and 2m were the most potent of the series tested and the parasites treated with these compounds exhibited ultrastructural changes, such as cell body shrinkage, loss of cellular membrane integrity, vacuolization of cytoplasm, membrane profiles surrounding organelles and swelling of mitochondria. The data showed that these compounds reduced the survival of intracellular amastigotes and presented low toxicity for mammalian cells. The compounds produced increased NO production compared to untreated cells in non-infected macrophages. Treated promastigote forms showed an increase in the number of cells stained with propidium iodide. The compounds brought about significant changes in mitochondrial membrane potential. According to the present study, phthalimido-thiazole compounds exhibit leishmanicidal activity and could be used to develop novel antileishmaniasis drugs and explore potential molecular targets.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutical Sciences - Volume 105, 15 July 2017, Pages 1-10
نویسندگان
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